B-207 Effect of Maternal Body Mass Index on Circulating Fetal DNA Concentration in Blood: Beyond Mere Dilution

Abstract Background Fetal DNA analysis in maternal blood has become a widely used, effective non-invasive prenatal testing method. However, circulating fetal DNA concentration is subject to variability due to several maternal factors, including gestational age, placental mass, and conditions such as high body mass index (BMI) and autoimmune diseases. An elevated maternal BMI is linked to higher levels of maternal DNA in the bloodstream, which can dilute the fetal DNA signal. This study employed the Y chromosome marker DYS14—virtually absent from the maternal genome—to investigate whether maternal BMI influences fetal DNA concentration beyond a mere dilution effect. Our goal was to determine whether maternal BMI directly impacts fetal DNA yield, which could affect the accuracy of fetal sex determination and other prenatal tests. Methods Data were retrieved from a private laboratory database specializing in fetal sex determination using quantitative PCR (qPCR). The assay specifically amplifies the DYS14 region of the Y chromosome, which is absent in the maternal genome, ensuring that the detected signal is uniquely fetal. The dataset included 1,395 cases with conclusive detection of the Y chromosome and associated data such as gestational age, cycle quantification (Cq) values, and maternal body mass index (BMI). Maternal BMI was categorized into three groups: normal (BMI < 25) n=719, overweight (25 = BMI < 30) n=440, and obesity (BMI = 30) n=236. Raw Cq values were transformed using the formula 2^(-Cq) to estimate fetal DNA concentration. Data normality was assessed using the Shapiro-Wilk test, which confirmed non-normal distribution for all groups. Group comparisons were made using the non-parametric Kruskal-Wallis test, and post hoc analyses were conducted using the Mann-Whitney U test with Bonferroni correction. All statistical analyses were performed using Python libraries, with significance set at p < 0.05. Results The median Cq values for the normal weight, overweight, and obesity groups were 32.60 (range: 30.09–34.91), 32.92 (range: 28.51–35.2), and 33.08 (range: 29.21–35.06), respectively. The Kruskal-Wallis test revealed significant differences between groups (p < 0.001). Post hoc analysis using the Mann-Whitney U test showed that the normal BMI group had significantly lower Cq values than both the overweight and obesity groups (p < 0.001 for both comparisons). Furthermore, the overweight group showed significantly lower Cq values than the obesity group (p = 0.014). Conclusion Our findings indicate that fetal DNA concentration in maternal blood is significantly affected by maternal BMI. Women with a normal BMI exhibited lower Cq values, reflecting higher fetal DNA concentration, compared to those who were overweight or obese. This suggests that the influence of maternal BMI on fetal DNA yield extends beyond a simple dilution effect caused by increased maternal DNA levels. Instead, maternal BMI appears to directly impact the amount of fetal DNA available, potentially through mechanisms affecting fetal DNA release or stability. These insights highlight the importance of considering maternal characteristics, such as BMI, when interpreting non-invasive prenatal assays. Adjusting for BMI could lead to more accurate fetal sex determination and other prenatal tests, ensuring greater reliability in clinical practice.